Physiological unloading of cardiopulmonary mechanoreceptors by posture changes does not influence the pressor response to isometric exercise in healthy humans

Summary In recent studies in humans the role of cardiopulmonary baroreflexes in modulating the cardiovascular responses to isometric exercise (somatic pressor reflex) has been investigated by performing static hand-grip exercise during deactivation of cardiopulmonary receptors produced by low levels of lower body negative pressure; however, findings from these studies have not been consistent. The purpose of this study was to investigate whether a more physiological unloading stimulus of cardiopulmonary baroreceptors, obtained by sequentially changing posture, could influence the pressor response to somatic afferent stimulation induced by isometric, exercise. To accomplish this, ten healthy subjects performed a 2-min isometric handgrip (IHG) at 30% maximal voluntary contraction after 10 min of supine rest and, in rapid sequence, after 10 min of sitting and 10 min of standing, at the time when, owing to their transitory nature, the cardiovascular effects, due to arterial baroreceptor intervention should have been minimal. During IHG arterial pressure (BP_a) was continuously and noninvasively measured to quantify accurately the blood pressure response to IHG both in magnitude and time course. Results showed that the pressor response to IHG was not significantly influenced by change in posture, either in magnitude or in time course. The mean arterial pressure increased by 17.4 (SEM 2.5), 18.6 (SEM 1.2) and 17.0 (SEM 1.3) mmHg in supine, sitting and standing [2.3 (SEM 0.3), 2.5 (SEM 0.2) and 2.3 (SEM 0.2) kPa] positions, respectively. Also the heart rate response to IHG was unaffected by change in posture. Most important, the sum of the separate BP_a responses induced by supine IHG and by posture change from supine to sitting (summation of reflexes) was not significantly different from the pressor response observed during sitting IHG (interaction of reflexes). Likewise, the sum of the separate BP_a. responses induced by sitting IHG and by changing postures from sitting to standing was not significantly different from the pressor response to standing IHG. These data indicate that, under physiological conditions, cardiopulmonary baroreflexes do not exert a significant role in modulating the reflex pressor drive from muscles during isometric exercise in healthy humans.     

XX sex reversal, palmoplantar keratoderma, and predisposition to squamous cell carcinoma: genetic analysis in one family

We describe a large inbred Sicilian family that includes four 46, XX (SRY-) brothers. Palmoplantar hyperkeratosis (PPK) and an associated predisposition to squamous cell carcinoma (SCC) of the skin, segregates as a recessive trait within the family. Interestingly, all the PPK-affected members of the family are phenotypic males (46,XY or 46,XX) while seven XX sibs are healthy phenotypic females with no signs of PPK. We propose that homozygosity for a single mutational event, possibly including contiguous genes, may cause PPK/SCC in both XY or XX individuals and sex reversal in XX individuals. The family is informative for linkage analysis for the PPK trait and allows linkage exclusion for the sex reversal trait. Here we show that 15 loci involved in PPK etiology, skin differentiation, function or malignancy, and nine loci involved in sex determination/differentiation are not implicated in the phenotype of this family.     

Antigenic characterisation of influenza B virus with a new microneutralisation assay: comparison to haemagglutination and sequence analysis

Although the haemagglutination inhibition assay is considered the "gold standard" for antigenic characterisation of influenza viruses, some limitations of this technique are well known. A new microneutralisation assay, as a tool for antigenic characterisation of influenza B viruses, has been standardised and its performance evaluated in comparison with the haemagglutination inhibition test in the light of molecular characterisation of the haemagglutinin. Twelve B viruses belonging to the two lineages and the four sub-lineages discriminated by phylogenetic analysis of HA were tested. The microneutralisation assay clearly distinguishes viruses belonging to different lineages and, in addition, discriminates strains belonging to different sub-lineages that are poorly or not discriminated using the haemagglutination inhibition test. This new microneutralisation assay could provide a useful tool for antigenic characterisation of circulating influenza viruses and contribute, together with the haemagglutination inhibition test and sequence analysis of the haemagglutinin and neuraminidase, in the choice of the strain for use in vaccine composition.     

Morphological variability of pterion in the human skull

The pterion is one of the most interesting bone meeting points in craniofacial osteology and its complex morphology derives from the fact that is the contact point of the facial skeletal elements, skull base and calvarium. Knowledge of its peculiar morphology is mandatory for the pterional approach used in microsurgery and surgery. The Authors studied 506 adult, human skulls where the pterion was accurately reconstructed on polyethylene sheets. They report their data on the morphological analysis and classify the forms. They focussed their attention on the presence of wormian bones at the level of the sphenoparietal suture, on the peculiar existing morphology and reviewed the literature on these classifications. The Authors also evaluated the length of the sphenoparietal suture, the minimum gap between the frontal and temporal, the influence of pteric bones on pterion variability and any correlations between measurements and cranial indexes.     

Neuropathological Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD) and Other Human Spongiform Encephalopathies (Prion Diseases)

Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: CJD - sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (PrP) immuno-reactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types). Gerstmann-Sträussler-Scheinker disease (GSS) (in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multicentric PrP plaques. Familial fatal insomnia (FFI) (in member of a family with PRNP178 mutation): thalamic degeneration, variable spongiform change in cerebrum. Kuru (in the Fore population). Without PrP data, the crucial feature is the spongiform change accompanied by neuronal loss and gliosis. This spongiform change is characterised by diffuse or focally clustered small round or oval vacuoles in the neuropil of the deep cortical layers, cerebellar cortex or subcortical grey matter, which might become confluent. Spongiform change should not be confused with non-specific spon-giosis. This includes status spongiosus (“spongiform state”), comprising irregular cavities in gliotic neuropil following extensive neuronal loss (including also lesions of “burnt-out” CJD), “spongy” changes in brain oedema and metabolic encephalopathies, and artefacts such as superficial cortical, perineuronal, or perivascular vacuolation; focal changes indistinguishable from spongiform change may occur in some cases of Alzheimer's and diffuse Lewy body diseases. Very rare cases might not be diagnosed by these criteria. Then confirmation must be sought by additional techniques such as PrP immunoblotting, preparations for electron microscopic examination of scrapie associated fibrils (SAF), molecular biologic studies, or experimental transmission.     

DNA cross-link-dependent RAD50/MRE11/NBS1 subnuclear assembly requires the Fanconi anemia C protein

Fanconi anemia (FA) is a cancer-predisposition syndrome characterized by hypersensitivity to interstrand-cross-link (ICL) inducers. FA hypersensitivity to ICL has been correlated with alterations in homologous recombination, non-homologous end-joining, telomere maintenance, DNA-damage assessment and checkpoint regulation, processes in which the components of the RAD50/MRE11/NBS1 (RMN) complex are involved. To better characterize the mechanisms by which ICL are processed in human cells and to gain insight into their toxicity in FA, we examined (i). the RMN complex assembling in response to the ICL inducers mitomycin C (MMC) and photoactivated 8-methoxypsoralen and (ii). the proficiency of FA cells to perform RMN activation in response to ICL inducers. We show here that ICL activates the assembly of the RMN proteins into subnuclear foci, and that their formation proceeds independently of ICL incision, a step mainly dependent on XP-F/ERCC1 heterodimer activity. Interestingly, FA cells were unable to form RMN foci in response to either ICL inducer. Analysis by pulsed-field gel electrophoresis and single-cell gel electrophoresis of MMC-treated cells showed that FA cells from complementation group C (FA-C cells, defective in the FANCC gene) form double-strand breaks and unhook MMC-induced ICL similarly to FANCC wild-type cells. These observations imply that the absence of RMN assembly in FA-C cells is not simply due to the absence of DNA ends produced as intermediates of ICL processing, and indicates a direct role for FANCC in RMN focus assembly in response to ICL inducers. Moreover, we show that the formation of foci, including BRCA1 and/or RAD51 proteins, is significantly delayed in FA cells. These alterations in the assembly of DNA-repair proteins in FA provide an interpretation for the DNA-damage processing anomalies observed in FA cells and for the genetic instability and the cancer predisposition of the syndrome.     

Social Distancing in Chronic Migraine during the COVID-19 Outbreak: Results from a Multicenter Observational Study

Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life.